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Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies

1
Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain
2
Immunology Unit, Department of Pathology, Hospital del Mar, 08003 Barcelona, Spain
3
Department of General Surgery, Breast Unit, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain
4
Oxford University Hospitals, NHS, Oxford OX3 9DU, UK
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(2), 392; https://doi.org/10.3390/cancers12020392
Received: 30 December 2019 / Revised: 3 February 2020 / Accepted: 6 February 2020 / Published: 8 February 2020
(This article belongs to the Special Issue PARPs, PAR and NAD Metabolism and Their Inhibitors in Cancer)
Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 are enzymes which post-translationally modify proteins through poly(ADP-ribosyl)ation (PARylation)—the transfer of ADP-ribose chains onto amino acid residues—with a resultant modulation of protein function. Many targets of PARP-1/2-dependent PARylation are involved in the DNA damage response and hence, the loss of these proteins disrupts a wide range of biological processes, from DNA repair and epigenetics to telomere and centromere regulation. The central role of these PARPs in DNA metabolism in cancer cells has led to the development of PARP inhibitors as new cancer therapeutics, both as adjuvant treatment potentiating chemo-, radio-, and immuno-therapies and as monotherapy exploiting cancer-specific defects in DNA repair. However, a cancer is not just made up of cancer cells and the tumor microenvironment also includes multiple other cell types, particularly stromal and immune cells. Interactions between these cells—cancerous and non-cancerous—are known to either favor or limit tumorigenesis. In recent years, an important role of PARP-1 and PARP-2 has been demonstrated in different aspects of the immune response, modulating both the innate and adaptive immune system. It is now emerging that PARP-1 and PARP-2 may not only impact cancer cell biology, but also modulate the anti-tumor immune response. Understanding the immunomodulatory roles of PARP-1 and PARP-2 may provide invaluable clues to the rational development of more selective PARP-centered therapies which target both the cancer and its microenvironment. View Full-Text
Keywords: PARP; immunomodulation; tumor microenvironment PARP; immunomodulation; tumor microenvironment
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Yélamos, J.; Moreno-Lama, L.; Jimeno, J.; Ali, S.O. Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies. Cancers 2020, 12, 392.

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